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Ewing’s sarcoma family of tumors (EFTs) is a group of rare and aggressive tumors. Data on EFTs in patients (pts) ≥ 50 years are limited and these pts are often not eligible for clinical trials. Some, but not all, studies have reported inferior outcome for older pts with EFTs. We conducted an IRB-approved retrospective analysis among centers of the French Sarcoma Group on pts diagnosed with EFTs at age ≥50 between 2000 and 2012. Clinical features, treatment modality and outcomes were analyzed. Seventy-seven pts were identified, including 36 females (46.8%) and the median age at diagnosis was 56 years (range: 50–86). The primary tumor was located in soft tissue in 59 pts (76.6%). Fifty-six pts (72.7%) had localized disease, among them 49 (87.5%) received chemotherapy in addition to local therapy. Their estimated 3-yr OS and event-free survival (EFS) rates were respectively 73.3% and 62.2%. Recurrence occurred in 43 pts. The estimated 3-yr OS rate was 37% in pts with metastatic disease at presentation. EFTs in pts ≥50 years are more likely to originate from soft tissue and their outcomes appear to be worse than that of younger pts treated with modern protocols.

Over 14 000 patients aged 15-24 are estimated to be diagnosed with cancer in the European Union (EU) each year. Teenagers and young adults (TYA) often fall down gaps between children's and adults cancer services. The specific challenges of providing optimal care to them are described, but we present a summary of recent progress. Progress to overcome these challenges is happening at different rates across Europe. We summarise the European national projects in this field but more recently we have seen the beginnings of European coordination. Within the EU 7th Funding Programme (FP7) European Network for Cancer Research in Children and Adolescents programme (ENCCA), a specific European Network for Teenagers and Young Adults with Cancer has held a series of scientific meetings, including professionals, patients and caregivers. This group has proposed unanswered research questions and agreed key features of a high-quality service that can improve outcomes for TYA with cancer, including the primacy of collaboration between adult and paediatric services to eliminate the gap in the management of TYA with cancer.

This phase II trial shows that sorafenib warrants further clinical exploration in advanced chordoma patients., Background There is no consensual treatment of locally advanced or metastatic chordomas. Patients and methods We conducted a multicenter, open-label, uncontrolled phase II trial of sorafenib (800 mg/day). The primary end point was the 9-month progression-free rate according to RECIST 1.1. All patients had documented progressive disease at the time of study entry. Results Twenty-seven patients were enrolled between May 2011 and January 2014. The median age was 64 (range, 30–86) years. There were 17 men and 10 women. Twelve patients had been previously treated with chemotherapy and molecularly targeted agents. The maximum toxicity grade per patient was grade 3 in 21 cases (77.8%) and grade 4 in 4 cases (14.8%). Sorafenib provided an intent-to-treat best objective response of 1/27 [3.7%; 95% confidence interval (CI) 0.1% to 19.0%], a 9-month progression-free rate of 73.0% (95% CI 46.1–88.0) and a 12-month overall survival rate of 86.5% (95% CI 55.8–96.5). Survival curves were similar in pretreated and not pretreated patients. Discussion Additional clinical trials further exploring sorafenib as a treatment of locally advanced or metastatic chordomas are warranted.

The purpose of this literature review is to make a point on the state of health of adolescents and young adults (15-25 years) suffering from cancer. The adaptation strategies and the impact of the announcement of cancer will be discussed. In addition, we are going to consider the characteristics of teenagers and young adults, given the fact that development is still in progress. This period is especially punctuated by various experiments and the emergence of some clinical signs. Also, we have identified various studies concerning the use of licit and illicit substances. Furthermore, we have taken interest in behavioral addictions, particularly cyber addiction. While trying to cross these variables with a population of teenagers and young adults in the context of somatic diseases, it occurred that this population was not well known and studied. The interest of this synthesis is to underline the importance to make future researches in these perspectives.

Ewing sarcoma is a primary bone tumor initiated by EWSR1–ETS gene fusions. To identify secondary genetic lesions that contribute to tumor progression, we performed whole-genome sequencing of 112 Ewing sarcoma samples and matched germline DNA. Overall, Ewing sarcoma tumors had relatively few single-nucleotide variants, indels, structural variants, and copy-number alterations. Apart from whole chromosome arm copy-number changes, the most common somatic mutations were detected in STAG2 (17%), CDKN2A (12%), TP53 (7%), EZH2, BCOR, and ZMYM3 (2.7% each). Strikingly, STAG2 mutations and CDKN2A deletions were mutually exclusive, as confirmed in Ewing sarcoma cell lines. In an expanded cohort of 299 patients with clinical data, we discovered that STAG2 and TP53 mutations are often concurrent and are associated with poor outcome. Finally, we detected subclonal STAG2 mutations in diagnostic tumors and expansion of STAG2-immunonegative cells in relapsed tumors as compared with matched diagnostic samples. Significance: Whole-genome sequencing reveals that the somatic mutation rate in Ewing sarcoma is low. Tumors that harbor STAG2 and TP53 mutations have a particularly dismal prognosis with current treatments and require alternative therapies. Novel drugs that target epigenetic regulators may constitute viable therapeutic strategies in a subset of patients with mutations in chromatin modifiers. Cancer Discov; 4(11); 1342–53. ©2014 AACR. This article is highlighted in the In This Issue feature, p. 1243

Background This retrospective multicenter study assessed the clinical, radiological and pathological presentation, treatment and outcome of 26 patients with Ewing-like sarcoma harboring BCOR-CCNB3 gene fusion transcript. Tumor samples had been collected between 1994 and April 2012. Procedure Eligibility criteria included assessment of a BCOR-CCNB3 transcript-positive tumor after molecular analysis and availability of minimal clinical and pathological data. Radiological data were also retrieved when possible. Data were analyzed by descriptive statistics and methods for survival analysis. Results Median age at diagnosis was 13.1 years (5.9 to 25.6 years). Most patients (24/26) had localized tumors. All tumors but five were localized to bone. CCNB3 immunochemistry showed strong nuclear staining on all samples. No specific radiological features were found. Most patients received chemotherapy (15 according to protocols designed for Ewing tumors), before and/or after local treatment (surgery and/or radiotherapy, with 46.2% receiving both). Local and metastatic relapses were of poor prognosis. Induction chemotherapy and treatment according to an Ewing protocol might influence survival for patients with localized tumors. Sixteen patients are alive in complete remission with a median follow-up of 86 months. Five year overall survival and disease-free survival were respectively 76.5% (95% CI, 58%–95%) and 67.9% (95% CI, 48%–88%). Conclusions BCOR-CCNB3 transcript-positive Ewing-like sarcoma diagnosis should be discussed for a transcript-negative small round cell sarcoma in a child, adolescent or young adult patient. Diagnosis needs to be stated through CCNB3 immunochemistry or transcript identification. The exquisite chemosensitivity of these tumors should encourage the use of polychemotherapy for appropriate care, associated with best local tumor control. Pediatr Blood Cancer 2014;61:2191–2198. © 2014 Wiley Periodicals, Inc.

Synovial sarcoma (SS) is a high-grade soft tissue sarcoma characterized by local invasiveness and a propensity to metastasize, affecting pediatric, adolescent, and adult populations. The peak incidence is observed in the third decade of life and SS is the most common nonrhabdomyosarcoma soft tissue sarcoma in childhood and adolescence. Although pediatric and adult SS appear clinically and radiologically identical, treatment modalities may differ according to the patient's age. For many years, pediatric oncologists have treated SS as a chemosensitive tumor according to the "rhabdomyosarcoma philosophy." In contrast, adult oncologists generally treat this tumor as a poorly chemosensitive tumor and focus on local control. The authors propose an update of SS in the pediatric population and analyze their results to those obtained in adults.

International audience; The skills of adult versus pediatric neuro-oncologists are not completely similar though additive. Because the tumors and their protocols are different and the tolerance and expected sequelae are specific. Multidisciplinary meetings including adult and pediatric neuro-oncologists are warranted to share expertise. Since 2008, a weekly national web based conference was held in France. Any patient with the following criteria could be discussed: Adolescent and Young Adults aged between 15 and 25 years, and any adult with a pediatric type pathology, including medulloblastoma, germ cell tumors, embryonic tumors, ependymoma, pilocytic astrocytoma.ResultsAttendance during the year 2015 was as follows: 42 meetings were held; the median number of cases discussed at each meeting was 4 (1 to 8); the mean number of attendants was 7 (2 to 12). One hundred and sixty-eight cases concerning 121 patients were discussed. Mean age was 30 years old (7 to 67). Forty-eight percent were discussed at diagnosis. The patients had mostly medulloblastomas (40%), germ cell tumors (11%), ependymomas (11%), pineal tumors (7%) and embryonal tumors (8%). The rate of inclusion in protocols was increased since the opening of this web conference, especially for the germ cell tumor SIOP protocol that is opened without age restriction, and in RSMA standard risk or MEVITEM relapse adult medulloblastoma protocols.ConclusionMultidisciplinary Web conference for AYAs is feasible and increases the inclusion rate in protocols. It should be developed further.; Les compétences en neuro-oncologie pédiatrique et adulte sont différentes mais complémentaires car les histologies, les protocoles thérapeutiques, la tolérance à court et moyen termes et les séquelles tardives attendues sont spécifiques à chaque tranche d’âge. Depuis 2008, ont été mises en place des réunions virtuelles nationales de concertation pluridisciplinaires hebdomadaires initialement dédiées aux adolescents et jeunes adultes (AJA) (15–25 ans) suspects ou porteurs d’une tumeur du système nerveux central dont l’incidence et l’expertise sont plus importantes en milieu pédiatrique. L’expertise a par la suite aussi bénéficié aux adultes plus âgés porteurs de ces affections. En 2015, 168 cas concernant 121 patients ont été discutés lors de 46 réunions. Le nombre moyen de dossiers discutés était de 4 (1 à 8). L’âge moyen de patients présentés était de 30 ans (7 à 67). Dans 48 % des cas, la discussion portait sur la prise en charge initiale. Le nombre moyen de thérapeutes présents était de 7 (2 à 12). Les histologies concernaient principalement des médulloblastomes 40 %, tumeurs germinales malignes 11 %, épendymomes 11 %, tumeurs pinétumeurs embryonnaires 8 %. La RCP AJA a donc prouvé la faisabilité et l’intérêt d’un échange centré sur cette sous-population, entre spécialistes de la neuro-oncologie d’origine diverses. Elle a permis d’optimiser la prise en charge de ces maladies orphelines, et l’inclusion dans des protocoles nationaux et internationaux, en particulier pour les tumeurs germinales malignes intracrâniennes ouverts à tous âges, et les protocoles s’adressant aux médulloblastomes en première ligne (RSMA) ou en rechute (MEVITEM).

// Loic Lebellec 1 , Francois Bertucci 2 , Emmanuelle Tresch-Bruneel 3 , Emmanuelle Bompas 4 , Yves Toiron 5 , Luc Camoin 5 , Olivier Mir 6 , Valerie Laurence 7 , Stephanie Clisant 8, 3 , Emilie Decoupigny 8 , Jean-Yves Blay 9 , Anthony Goncalves 5 , Nicolas Penel 1, 3 1 Department of Medical Oncology, Centre Oscar Lambret, Lille, France 2 Department of Medical Oncology, Institut Paoli-Calmette, Marseille, France 3 SIRIC OncoLille, Clinical Research and Methodological Platform, Lille, France 4 Department of Medical Oncology, Centre Rene Gauducheau, Nantes, France 5 Department of Molecular Pharmacology, Cancer Research Center of Marseille, Institut Paoli Calmettes, Marseille, France 6 Department of Medical Oncology, Gustave Roussy, Villejuif, France 7 Department of Medical Oncology, Institut Curie, Paris, France 8 Clinical Research Unit, Centre Oscar Lambret, Lille, France 9 Department of Medical Oncology, Centre Leon Berard, Lyon, France Correspondence to: Nicolas Penel, email: n-penel@o-lambret.fr Keywords: chordoma, sorafenib, biomarker, placental growth factor, vascular endothelial growth factor Received: March 31, 2016 Accepted: September 13, 2016 Published: September 21, 2016 ABSTRACT Background: Patients with advanced chordoma are often treated with tyrosine kinase inhibitors without any predictive factor to guide decision. We report herein an ancillary analysis of the the Angionext phase II trial (NCT 00874874). Results: From May 2011 to January 2014, 26 were sampled. The 9-month PFS rate was 72.9% (95%-CI: 45.9-87.9). During sorafenib treatment, a significant increase in PlGF (18.4 vs 43.8 pg/mL, p 1.04 ng/mL (HR=12.5, 95%-CI: 1.37-114, p=0.025) and VEGF at D7 >1.36 ng/mL (HR=10.7, 95%-CI: 1.16-98, p=0.037) were associated with shorter PFS. The 9-month PFS rate was 92.3% (95%-CI: 56.6-98.9) when VEGF at D1 was ≤1.04 ng/mL versus 23.3% (95%-CI: 1.0-63.2) when >1.04 ng/mL. Patients and Methods: Chordoma patients were treated with sorafenib 800 mg/day for 9 months, unless earlier occurrence of progression or toxicities. Six biomarkers (sE-Selectin, VEGF, VEGF-C, placental growth factor (PlGF), Thrombospondin, Stem Cell Factor (SCF)) were measured at baseline (day 1: D1) and day 7 (D7). Conclusion: High levels of VEGF was associated with poor outcome.

Given the excellent survival rate of children and teenagers treated for cancer, careful should be given in order to minimize long-term late effects of treatments and to improve quality of life. In this regard, fertility preservation is particularly important. Age, sex and concomitant therapies have an impact on the level of risk of hypofertility, with a stronger risk for chemotherapeutic regimens including alkylating agents, and gonads or hypothalamo-pituitary axis radiotherapy. Assessment of gonadotoxic impact of treatment strategy and fertility preservation techniques are crucial for limiting late effects. The objective of this literature review is to develop guidance for pediatric oncologists and hematologists relative to fertility preservation methods, in children and teenagers receiving gonadotoxic treatment. Specific follow-up after treatment is also proposed.

La preservation de la fertilite des jeunes patients traites par chimiotherapie, chirurgie ou radiotherapie est une preoccupation constante des oncologues. La congelation de sperme est une technique validee, facilement realisable et accessible en theorie a tout jeune homme pubere physiquement capable d’ejaculer. Pourtant, les oncologues et en particulier les pediatres rencontrent des difficultes a aborder cette question avec les adolescents et leur famille. Devant ce constat, un livret d’information intitule « Le CECOS c’est quoi ? » a ete realise avec l’aide d’adolescents. Grâce a un financement de la Ligue contre le cancer, dans le cadre des appels d’offres « adolescents et cancer », ce livret a pu etre distribue dans les services d’oncologie pediatrique francais (centres SFCE pour Societe francaise du cancer de l’enfant). Dans quatre d’entre eux, un questionnaire de satisfaction a ete donne avec le livret. Nous rapportons ici les resultats de l’analyse des questionnaires de satisfaction distribues, ainsi que les resultats d’une enquete nationale realisee aupres des centres d’oncologie pediatrique de la SFCE afin d’apprehender le niveau d’information des praticiens concernant l’existence de ce livret et leur satisfaction depuis sa mise a disposition. Les resultats de ces deux enquetes sont tres positifs et les adolescents comme les medecins reconnaissent la pertinence et l’utilite de cet outil.

Background Although the taxanes paclitaxel and docetaxel are among the most active agents for the treatment of a wide range of cancers, tumours often develop resistance to these treatments. Cabazitaxel is a novel taxane active in both preclinical models of chemotherapy-sensitive and -resistant human tumours and patients with advanced prostate cancer that progressed following docetaxel treatment. Aim To establish the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cabazitaxel. Patients and methods Cabazitaxel was administered every 3 weeks to patients with advanced solid tumours. The design allowed intrapatient dose escalation. The primary objective was to determine the MTD. Secondary objectives were to describe the safety profile, establish an appropriate dose, determine the pharmacokinetic (PK) profile of cabazitaxel, and assess antitumour activity. Results Twenty-one patients were recruited. The MTD was reached at 30 mg/m2, at which three of five patients experienced haematologic DLTs during the first cycle. DLTs during subsequent cycles were mainly haematologic and reported at 25 and 30 mg/m2 dosing levels. Nail disorders and severe alopecia were not reported, and neurotoxicity, fluid retention and hypersensitivity were mild and infrequent. Cabazitaxel demonstrated linear PK, a triphasic elimination profile, with a long half-life and high clearance. Of the 19 patients evaluable for response, one unconfirmed partial response and six occurrences of stable disease were reported. Conclusions The 25 mg/m2 dose of cabazitaxel was recommended for use in future clinical studies. In this study, cabazitaxel had an acceptable tolerability profile and activity in cervical, colorectal, endometrial and lung cancers.

Carcinomas are rare tumors of the adolescent-young adult (AYA) with a different spectrum from those of adults. The most common sites outside of the thyroid is the nasopharynx, salivary gland, colon-rectum and ovaries. If nasopharyngeal carcinoma or salivary gland tumors are good prognosis, others are more reserved prognosis, such as digestive carcinomas, gynecological or midline. The revelation modes are non-specific and depend on the location: mass, tumor syndrome, pain, impaired general condition. The unusual of pediatric carcinomas led to propose a systematic oncogenetic exploration. The medical history of the family, the symptoms and the type of the carcinoma should guide the analysis. In the absence of guidance, analysis of TP53 gene and, for carcinomas of the expanded spectrum of the hereditary non-polyposis colorectal cancer (HNPCC) syndrome, the search for mutation of MMR genes (mismatch repair) seems essential. Because of the rarity of these diseases and the absence of homogeneous recommendations, members of the rare tumors committee of the SFCE recommended for the management of these AJA, an histological review by a pathologist familiar with carcinomas of the adult, a double discussion between pediatric and adult oncologists, analysis of adult standards with adaptation to pediatric data, especially in terms of risk of side effects. An advice to a national opinion (by a member of FRACTURE group) or European (group EXPERT) is sometimes necessary in the most complex situations.

The pattern of cancer seen in young people changes with increasing age, transitioning from childhood- to adult-type cancer in adolescence and the third decade. The risk factors, presentation and biology of cancer in young adults differ from those in the older adult population. Factors of particular significance in adolescents and young adults (AYAs) include genetic predisposition to adult-type cancer, diagnostic uncertainty, long-term morbidity and considerations of fertility. New systemic therapies are being introduced that can prolong life and even increase the chance of cure, but the impact on AYAs is uncertain, as these patients are often under-represented in clinical trials. Here, we discuss the management of AYAs with 3 of the most common cancers affecting adults, when they emerge in the AYA populations, and therefore are currently met by medical oncologists - breast cancer, colorectal cancer and melanoma.

In France, although children aged less than 15 years with cancer are usually referred to pediatric oncology centers, adolescents may be treated at pediatric or adult oncology centers. The objective was to compare survival according to their site of treatment.Using population-based registration, 15- to 19-year-old patients diagnosed with cancer in 2006 or 2007 and living in six French regions (accounting for 41% of the French population) were included.Of the 594 patients included, 33% of the French adolescents were treated at a pediatric oncology center. Compared with those treated at a pediatric center, adolescents treated at an adult center were older, were more likely to have carcinoma and germ-cell tumor, had a longer time to diagnosis, and were less likely to be enrolled in a clinical trial. In addition, the decisions for their management were less likely to be taken in the context of multidisciplinary team meetings. In multivariate analysis, adolescent patients treated at a pediatric center did not have significantly different overall survival (OS) compared with those treated at an adult center (5-year OS: 84.1% [95% confidence interval: 78.6-90.0] versus 87.7% [95% confidence interval: 84.2-91.3]; P = 0.25).The outcomes of French adolescents with cancer have begun to improve, with 81.2% survival in 2006-2007, with no difference between the types of treatment center. However, for this unique group of diseases, survival is not the unique endpoint. In order to ensure good quality of life after cancer, management of those patients requires specific approaches, designed to reduce the late effects of cancer treatment and improve supportive care.

Survival of children and adolescents and young adults (AYAs) treated for cancer has increased with improved treatments. However, there is still an increased risk of second primary cancer (SPC) in the long term compared with the same-age population, especially related to treatments. The follow-up of this population and the prevention of SPC are important issues. Therefore, this study aimed to review the available literature on cancer risk factors (lifestyle and occupational exposures) in children and AYAs previously treated for cancer in order to identify interventions that might be implemented to improve healthy behaviors in this population.PubMed was searched using the following terms: "cancer[Tiab] AND young adult[Tiab] or teen[Tiab] or childhood[Tiab] AND prevention[Tiab] AND survivors[Meshterm]."Twenty-seven articles were included. Children and AYA survivors of cancer have similar risk behaviors to their peers regarding tobacco, diet, and sun exposure. However, they have lower physical activity. Few studies on prevention strategies in this population were identified. Results of available studies remain inconclusive. No publications were found on occupational exposure and risk of second cancer.Children and AYAs treated for cancer are a population at risk and require specific effective prevention strategies.

The pattern of cancer seen in young people changes with increasing age, transitioning from childhood- to adult-type cancer in adolescence and the third decade. The risk factors, presentation and biology of cancer in young adults differ from those in the older adult population. Factors of particular significance in adolescents and young adults (AYAs) include genetic predisposition to adult-type cancer, diagnostic uncertainty, long-term morbidity and considerations of fertility. New systemic therapies are being introduced that can prolong life and even increase the chance of cure, but the impact on AYAs is uncertain, as these patients are often under-represented in clinical trials. Here, we discuss the management of AYAs with 3 of the most common cancers affecting adults, when they emerge in the AYA populations, and therefore are currently met by medical oncologists - breast cancer, colorectal cancer and melanoma.

Background In France, as in other countries, there is a need for a population-based view of access to care and modalities of treatment for adolescents with cancer. Procedure Using a population-based registration, we report pathways of care for 15–19-year-old patients, diagnosed with cancer in 2006 and 2007, living in six French regions, accounting for 41% of the French population. Results The median times (inter-quartile range) for diagnosis and treatment of the 594 included adolescents were 8 weeks (3–17) and 3 days (0–16), respectively. First physicians met by the patients were mostly general practitioners (59%). Seventeen percent of patients were firstly seen on emergency wards. Most of the patients (82%) were treated in an adult environment. Management decisions were taken within the context of a multi-disciplinary team (MDT) in 54% of cases. Twenty-seven percent of patients were included in randomized or non-randomized clinical studies: percentage depended on the tumor type and on the number of on-going trials at the study period. Fifteen percent of patients were included in pediatric studies, 7% in adult studies, and 5% in studies including both adults and children. Conclusions The pathways of care for French adolescent patients with cancer are heterogeneous. Our results reveal differences in MDT meetings according to tumor types and a lack of effective collaboration between pediatric and adult wards. Efforts must be made to develop cancer networks to ensure that adolescents receive the optimal care in a suitable environment. Pediatr Blood Cancer 2012; 58: 924–929. © 2011 Wiley Periodicals, Inc.

Background The presence of the EWS-WT1 gene fusion transcript (GFT) is characteristic of desmoplastic small round cell tumor (DSRCT), a rare and very aggressive disease for which the treatment has not yet been clearly standardized. Methods This was a retrospective national multicenter analysis of young patients

La population des adolescents et jeunes adultes (AJA) en France a peu beneficie des progres de la cancerologie ces dernieres decennies. Malgre tout, les etudes epidemiologiques et les publications recentes dans le domaine du cancer concernant cette tranche d’âge se multiplient depuis peu. Il en ressort l’identification de besoins specifiques, tant en termes de soins oncologiques et complementaires, que de prise en charge psychosociale pendant et apres la fin du traitement. Seule une amelioration de la structuration des soins, et notamment du lien entre medecine adulte et pediatrique les concernant, permettra de faire progresser les resultats en termes de survie mais aussi de bien-etre physique et psychique a court et a long terme chez ces patients.

Resume Le cancer du sein est la cause la plus frequente de meningite carcinomateuse (MC) parmi les tumeurs solides. Cette serie monocentrique rapporte les caracteristiques de 91 patientes presentant une meningite carcinomateuse d’un cancer du sein traite par methotrexate intrathecal (MTX) entre 2000 et 2007. Un traitement intrathecal par : MTX (15 mg/j ; j1 a j5), depomedrol (40 mg ; j1) et acide folinique (12 mg IV ou 25 mg PO ; j1 a j5) etait administre toutes les deux semaines. La survie des patientes a ete analysee en fonction des caracteristiques de leur tumeur et de la reponse clinique et biologique au traitement. La survie mediane etait de 4,5 mois (0-53). En analyse multivariee, les facteurs de mauvais pronostic lors du diagnostic sont : l’OMS > 2 ( p = 0,006, RR = 0,33 [0,15-0,71]), plus de trois lignes de chimiotherapie avant le diagnostic ( p = 0,03, RR = 0,40 [0,19-0,93]), l’absence de recepteurs hormonaux sur la tumeur initiale [ p = 0,02, RR = 0,4 [0,19-0,90]) et un dosage eleve du cyfra-21-1 dans le LCR ( p = 0,048, RR = 0,09-0,99). La progression clinique apres un cycle et la reponse biologique apres deux cycles etaient correles de maniere independante a la survie globale ( p p = 0,003, RR = 3,6 [1,5-8,5], respectivement). Un score ayant pour but de definir trois groupes de patientes est propose. Conclusion Le pronostic des patientes atteint de MC est mauvais mais 25 % des malades sont encore en vie a un an. Ce score pronostique pourrait aider a la decision therapeutique apres avoir ete valide dans d’autres etudes cliniques.

Aim Phase I study of seliciclib (CYC202, R-roscovitine), an inhibitor of cyclin-dependent kinases 2, 7 and 9, causing cell cycle changes and apoptosis in cancer cells. Patients and methods This phase I trial aimed at defining the toxicity profile, the maximum tolerated dose (MTD), the recommended phase II dose (RD) and the main pharmacokinetic and pharmacodynamic parameters of oral seliciclib. Three schedules were evaluated: seliciclib given twice daily for 5 consecutive days every 3 weeks (schedule A), for 10 consecutive days followed by 2 weeks off (schedule B) and for 3 d every 2 weeks (schedule C). Results Fifty-six patients received a total of 218 cycles of seliciclib. Dose-Limiting Toxicities (DLT) consisting of nausea, vomiting, asthenia and hypokalaemia occurred at 1600 mg bid for schedule A and in schedule C, DLT of hypokalaemia and asthenia occurred at 1800 mg bid. The evaluation of longer treatment duration in schedule B was discontinued because of unacceptable toxicity at lower doses. Other adverse events included transient serum creatinine increases and liver dysfunctions. Pharmacokinetic data showed that exposure to seliciclib and its carboxylate metabolite increased with increasing dose. Soluble cytokeratin 18 fragments allowed monitoring of seliciclib-induced cell death in the blood of patients treated with seliciclib at doses above 800 mg/d. One partial response in a patient with hepatocellular carcinoma and sustained tumour stabilisations were observed. Conclusions The MTD and RD for seliciclib are 1250 mg bid for 5 d every 3 weeks and 1600 mg bid for 3 d every 2 weeks, respectively.

Background: Breast cancer is the leading nonhematologic cause of meningeal carcinomatosis (MC). The aim of this study was to report the outcome of patients diagnosed with breast cancer MC and treated in single institution by a high-dose intrathecal methotrexate (MTX) regimen. Methods: Ninety-one patients were diagnosed with breast cancer MC from 2000 to 2007. Intrathecal treatment was MTX 15 mg/day (days 1-5), hydrocortisone acetate (day 1) and oral folinic acid (days 1-5), repeated every 2 weeks. Patients and tumor characteristics were associated with the early clinical and biological outcome and with the overall survival (OS). Results: The median survival was 4.5 months (range 0-53). In multivariate analysis, adverse prognostic factors at diagnosis were performance status >2 [P = 0.006, response rate (RR) = 0.33 (0.15-0.71)], more than three chemotherapy regimens before MC diagnosis [P = 0.03, RR = 0.40 (0.19-0.93)], negative hormone receptor status [P = 0.02, RR = 0.4 (0.19-0.90)] and high Cyfra 21-1 level [P = 0.048, RR = (0.09-0.99)]. Clinical progression after one cycle and biological response after two cycles were independently associated with OS [P < 0.001, RR = 0.09 (0.02-0.37) and P = 0.003, RR = 3.6 (1.5-8.5), respectively]. We propose a prognostic score in order to define three distinct groups of prognosis. Conclusions: MC presents a poor prognosis, but 1-year survival rate was 25%. This score may become a useful tool for treatment decision and clinical trials.

Ewing sarcoma (EWS) is a rare pediatric tumor predominantly occurring in children of European ancestry and is characterized by the pathognomonic EWSR1-FLI1 fusion oncogene. To identify germline susceptibility loci associated with EWS risk, we performed a genome-wide association study (GWAS) meta-analysis of 749 EWS cases and 1,378 unaffected individuals of European ancestry from sample collections within the Institut Curie, National Cancer Institute and the Childhood Cancer Survivor Study. Our study replicated previously reported susceptibility loci at 1p36.22, 10q21.3 and 15q15.1 as well as identified novel loci at 6p25.1, 8q24.23, 20p11.22 and 20p11.23 (P-values Citation Format: Mitchell J. Machiela, Thomas G. Grünewald, Didier Surdez, Stephanie Reynaud, Olivier Mirabeau, Eric Karlins, Rebeca Alba Rubio, Sakina Zaidi, Sandrine Grossetete-Lalami, Stelly Ballet, Eve Lapouble, Valérie Laurence, Jean Michon, Gaelle Pierron, Heinrich Kovar, Nathalie Gaspar, Udo Kontny, Anna González-Neira, Piero Picci, Javier Alonso, Ana Patino-Garcia, Nadège Corradini, Neal D. Freedman, Nathaniel Rothman, Casey L. Dagnall, Laurie Burdette, Kristine Jones, Michelle Manning, Kathleen Wyatt, Weiyin Zhou, Meredith Yeager, David G. Cox, Robert N. Hoover, Javed Khan, Gregory T. Armstrong, Wendy M. Leisenring, Smita Bhatia, Leslie L. Robison, Uta Dirksen, Markus Metzler, Wolfgang Hartmann, Konstantin Strauch, Thomas Kirchner, Andreas E. Kulozik, Lindsay M. Morton, Lisa Mirabello, Margaret A. Tucker, Franck Tirode, Stephen J. Chanock, Olivier Delattre. Multiple new susceptibility loci identified in genome-wide association study of Ewing sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2970.

Rhabdoid tumours (RTs) are rare but highly aggressive tumours of childhood. Their rarity and their miscellaneous locations make the diagnosis particularly challenging for pathologists. Central nervous system and peripheral RTs have been associated with biallelic inactivation of the hSNF5/INI1/SMARCB1 (hSNF5/INI1) tumour suppressor gene. Immunohistochemistry (IHC) with a monoclonal anti-hSNF5/INI1 antibody has recently been proposed as an efficient diagnostic tool for RTs. We have conducted a retrospective study of 55 tumours referred to our institution with a suspicion of RT. This analysis included pathological review, IHC with anti-hSNF5/INI1 antibody, and molecular investigation using quantitative DNA fluorescent analysis and sequencing of the nine exons of hSNF5/INI1. The molecular lesion could be detected in 37 of the 39 cases exhibiting negative staining for hSNF5/INI1. In the two discrepant cases, the lack of detection of genetic abnormality was probably owing to the presence of a high number of non-tumour cells in the samples. This indicates that hSNF5/INI1 IHC is very sensitive and highly specific for the detection of hSNF5/INI1 loss-of-function. Among the 38 cases with typical RT histological features, six failed to exhibit hSNF5/INI1 mutation and stained positive for hSNF5/INI1. This strongly supports the evidence of a second genetic locus, distinct from hSNF5/INI1, associated with RT. Conversely, seven tumours with histological features poorly compatible with RT stained negative for hSNF5/INI1; they nevertheless exhibited an age of onset and a clinical behaviour similar to RT. This suggests that hSNF5/INI1 inactivation is not strictly limited to typical RT but characterizes a wider family of hSNF5/INI1-deficient tumours. Consequently, we believe that anti-hSNF5/INI1 IHC should be performed widely, even when the pathological characteristics are not typical. The molecular investigation should be performed in infants when a rhabdoid predisposition syndrome is suspected. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The purpose of this literature review is to make a point on the state of health of adolescents and young adults (15-25 years) suffering from cancer. The adaptation strategies and the impact of the announcement of cancer will be discussed. In addition, we are going to consider the characteristics of teenagers and young adults, given the fact that development is still in progress. This period is especially punctuated by various experiments and the emergence of some clinical signs. Also, we have identified various studies concerning the use of licit and illicit substances. Furthermore, we have taken interest in behavioral addictions, particularly cyber addiction. While trying to cross these variables with a population of teenagers and young adults in the context of somatic diseases, it occurred that this population was not well known and studied. The interest of this synthesis is to underline the importance to make future researches in these perspectives.

La survie des enfants traites pour un cancer a considerablement augmente ces 30 dernieres annees grâce aux progres therapeutiques rendus possibles par une approche multidisciplinaire cooperative, nationale et internationale. Il est desormais possible, dans un nombre non negligeable de situations cliniques, d’envisager une desescalade therapeutique prudente. A l’inverse, certains patients requierent des therapeutiques lourdes grevees de sequelles parfois invalidantes. Dans tous les cas, l’administration de therapeutiques cytotoxiques, de rayonnement ionisant ou la realisation d’un geste chirurgical potentiellement mutilant imposent la mise en place d’un suivi au long court. Nous presentons ici les sequelles attendues des therapeutiques anticance reuses employees chez l’enfant. Nous evoquons la prise en charge diagnostique et therapeutique optimale de ces complications chez de jeunes patients en cours de croissance.

Purpose: The purpose of this study was to investigate the safety and tolerability of MS209, a potent inhibitor of P-glycoprotein, when given in combination with docetaxel and to determine whether MS209 affects docetaxel pharmacokinetics. Experimental design: Patients with advanced solid malignancies were eligible for this phase I trial. Docetaxel as 1-hour infusion was given alone during the first cycle. MS209 was introduced as of cycle 2 and given orally 30 minutes after docetaxel infusion. The dose escalation scheme followed a modified Fibonacci model with six steps (docetaxel, 60-100 mg/m2 and MS209, 300-1,200 mg per body). Results: A total of 30 patients were treated at five dose levels. Dose-limiting toxicities were febrile neutropenia, infection, stomatitis, dysphagia, and fatigue. The maximum tolerated dose was reached at level 5 (docetaxel, 80-MS: 1,200). Pharmacokinetic analysis failed to show a strong pharmacokinetic interaction between the two compounds, but at the highest dose levels, there is a trend to an increase of docetaxel AUC when this agent is given in combination with MS209. Conclusion: MS209 can be given in combination with docetaxel, with limited effect on docetaxel toxicity or pharmacokinetics.

This trial assessed pharmacokinetic interactions between cetuximab and irinotecan. Patients were placed in either in group A (irinotecan 350 mg/m2/3 weeks and 400 mg/m2 cetuximab at week 2 then 250 mg/m2/week) or group B (cetuximab weekly starting week 1 then irinotecan starting week 4). Patient plasma or serum samples from each treatment arm were analysed using HPLC and ELISA. Among 14 patients, compartmental model showed no significant differences in mean plasma AUC at week 1 versus week 4 for irinotecan (44,388 versus 39,800 microg/ml/h) and cetuximab (20,441 versus 23,363 microg/ml/h), respectively. Half-lifes (standard deviations) for irinotecan were 16.02 (+/-8.41) h at week 1 and 13.99 (+/-2.14) h at week 4, and for cetuximab 106 (+/-32) at week 3 and 111 (+/-30) h at week 4. Mean concentration-versus-time profiles either alone or in combination were superimposable for cetuximab and irinotecan. From this study, we conclude that there is no evidence of pharmacokinetic interaction between irinotecan and cetuximab.

Ewing tumors remain of poor prognosis, with 5-year overall survival of 55% to 65% in localized patients and not exceeding 25% in primarily metastatic disease. Several reports, mainly in children, have reported that some patients with poor-risk Ewing tumors may benefit from high-dose chemotherapy (HDCT) with autologous stem cell rescue. This retrospective study analyzed 46 patients treated in our institution between 1987 and 2000 for localized or primary metastatic Ewing tumors by HDCT followed by stem cell rescue. Median follow up was 7.1 years. Median age was 21 years (range, 15-46 years). Twenty-two percent of patients had metastases at diagnosis. The tumor site was axial in 56% of patients. Median tumor size was 9.5 cm. The treatment regimen consisted of induction chemotherapy, local treatment, maintenance chemotherapy, and consolidation HDCT based on alkylating agents. No toxic death was observed in the intensive therapy phase. Five-year overall survival and progression-free survival were 63 +/- 7.7% and 47 +/- 7.6%, respectively. Pejorative prognostic factors in this population were metastases at diagnosis (5-year overall survival 34% vs.71%, P = 0.017) and poor pathologic response (5-year overall survival 44% vs.77%, P = 0.03). This retrospective study shows a high long-term survival rate with high-dose chemotherapy in adults.

Adolescence can be an extremely stressful time for all concerned. When this period is then compounded by the development of cancer, formidable and seemingly insurmountable problems may be perceived. Cancer in adolescence is relatively uncommon, with an annual incidence rate in western populations of approximately 150-200 per million. Five-year survival of patients diagnosed around 1990 exceeded 70% in the United Kingdom (UK) and United States of America (USA), and adolescents with cancer are likely to remain fertile. Further advances in therapeutic modalities are creating a generation of adolescents and young adults with cancer who can now aspire to the same sexual and reproductive activities as their healthy peers. This then raises the issue of avoidance of undesired pregnancy during and after treatment. This article aims to address the contraceptive needs of adolescents and young adults undergoing treatment for cancer.

The aim of this study was to define the characteristics of patients with idiopathic thrombocytopenic purpura (ITP) and breast cancer and discuss the relationship between these two diseases. Ten patients treated for breast cancer and presenting with ITP were screened for this study. The diagnosis of breast cancer was confirmed by biopsy or surgical sample. The diagnosis of ITP was defined by 1) platelet count less than 140.10(9)/l with normal or increased number of megakaryocytes on bone marrow aspirate, 2) after exclusion of thrombocytopenia-induced medication or disorders, and 3) absence of splenomegaly. ITP was diagnosed before breast cancer in three cases, concomitantly in three, and after the diagnosis of breast cancer in four cases. Platelet count and breast cancer showed an independent course in seven cases, and appeared to be correlated in the other three patients. No correlation was found between the development of ITP and tumor characteristics. In contrast, the median platelet count was 15.10(9)/l (range 3-26) for the 3 patients with a correlation between the course of ITP and breast cancer evolution and 70.10(9)/l (range 20-90) for the other cases (p = 0.05, Mann-Whitney U test). Breast cancers are associated with ITP, with a parallel course of the two diseases in one third of cases. This may suggest tumor-induced immunologic thrombocytopenia.

The aim of this retrospective study was to assess predictive factors for clinical response to preoperative chemotherapy and prognostic factors for survival. From 1981 to 1992, 936 patients with T2-T3, N0-N1 breast cancer who received 2–6 months (median 4) of preoperative chemotherapy were selected from the Institute Curie database. Preoperative treatment was followed by surgery and/or radiotherapy. Median follow-up was 8.5 years (range 7–211 months). The objective response rate before surgery and/or radiotherapy was 58.3%. In stepwise multivariate analysis (Cox model), favourable prognostic factors for survival were the absence of pathological axillary lymph node involvement (Relative Risk (RR) 1.54; P=0.0004), low histological tumour grade (RR=1.54; P=0.0017), clinical response to preoperative chemotherapy (RR=1.45, P=0.0013), positive progesterone receptor (PR) status (RR=1.56; P=0.0001), smaller tumour size (RR=1.37; P=0.005) and lack of clinical lymph node involvement (RR=1.42; P=0.007). The association of clinical tumour response with survival is independent of the baseline characteristics of the tumour. Clinical response could be used as a surrogate marker for evaluation of the efficacy of neoadjuvant chemotherapy before assessment of the pathological response.

This retrospective multicenter study assessed the clinical, radiological and pathological presentation, treatment and outcome of 26 patients with Ewing-like sarcoma harboring BCOR-CCNB3 gene fusion transcript. Tumor samples had been collected between 1994 and April 2012.Eligibility criteria included assessment of a BCOR-CCNB3 transcript-positive tumor after molecular analysis and availability of minimal clinical and pathological data. Radiological data were also retrieved when possible. Data were analyzed by descriptive statistics and methods for survival analysis.Median age at diagnosis was 13.1 years (5.9 to 25.6 years). Most patients (24/26) had localized tumors. All tumors but five were localized to bone. CCNB3 immunochemistry showed strong nuclear staining on all samples. No specific radiological features were found. Most patients received chemotherapy (15 according to protocols designed for Ewing tumors), before and/or after local treatment (surgery and/or radiotherapy, with 46.2% receiving both). Local and metastatic relapses were of poor prognosis. Induction chemotherapy and treatment according to an Ewing protocol might influence survival for patients with localized tumors. Sixteen patients are alive in complete remission with a median follow-up of 86 months. Five year overall survival and disease-free survival were respectively 76.5% (95% CI, 58%-95%) and 67.9% (95% CI, 48%-88%).BCOR-CCNB3 transcript-positive Ewing-like sarcoma diagnosis should be discussed for a transcript-negative small round cell sarcoma in a child, adolescent or young adult patient. Diagnosis needs to be stated through CCNB3 immunochemistry or transcript identification. The exquisite chemosensitivity of these tumors should encourage the use of polychemotherapy for appropriate care, associated with best local tumor control.

The aim of this study was to evaluate the feasibility of a high-dose intensity and high-dose density multicycle epirubicin and cyclophosphamide regimen with peripheral blood stem cells (PBSC) and haematopoietic growth factor (G-CSF) support in advanced breast cancer patients. From August 1994 to September 1999, 56 breast cancer patients (8 stage IIIB and 48 stage IV) received 205 courses of cyclophosphamide 3 g x m(-2) and epirubicin 100 mg x m(-2) every 14 days. G-CSF 5 microg x kg(-1) x day(-1) was administered from day 3 to neutrophil recovery. 4 courses were planned. PBSC were collected after course 1, and reinfused after courses 3 and 4, withor = 2 x 10(6) CD34+ PBSC x kg(-1) required for each reinfusion. 48 patients (86%) received all 4 planned courses. Early withdrawal was consecutive to infectious complications (n = 4), severe asthenia (n = 3), haemorrhagic cystitis (n = 1). A median number of 10.8 x 10(6) CD34+ PBSC x kg(-1) (range, 3-80) was harvested with 1 or 2 apheresis in 48 patients (94%). Median relative dose intensity was 91.3% (range, 72-102%). Grade 4 neutrophil toxicity was observed in 100% of patients. Febrile neutropenia was observed in 40% of courses (median duration 2 days). Red blood cells and platelets had to be transfused in 54% and 27% of courses, respectively. There were no toxic deaths. Objective response rate was 69% in stage IV patients (31/45 evaluable pts), with a 16% complete response rate. Their median progression-free and overall survivals were 22.5 and 37 months, respectively. This epirubicine-containing high-dose regimen appeared feasible, albeit with high toxicity. Time-related progression parameters exceed commonly reported ones. Controlled studies of upfront sequential high-dose chemotherapy are still needed to evaluate its real benefit.

Background In France, although children aged less than 15 years with cancer are usually referred to pediatric oncology centers, adolescents may be treated at pediatric or adult oncology centers. The objective was to compare survival according to their site of treatment. Procedure Using population-based registration, 15- to 19-year-old patients diagnosed with cancer in 2006 or 2007 and living in six French regions (accounting for 41% of the French population) were included. Results Of the 594 patients included, 33% of the French adolescents were treated at a pediatric oncology center. Compared with those treated at a pediatric center, adolescents treated at an adult center were older, were more likely to have carcinoma and germ-cell tumor, had a longer time to diagnosis, and were less likely to be enrolled in a clinical trial. In addition, the decisions for their management were less likely to be taken in the context of multidisciplinary team meetings. In multivariate analysis, adolescent patients treated at a pediatric center did not have significantly different overall survival (OS) compared with those treated at an adult center (5-year OS: 84.1% [95% confidence interval: 78.6–90.0] versus 87.7% [95% confidence interval: 84.2–91.3]; P = 0.25). Conclusions The outcomes of French adolescents with cancer have begun to improve, with 81.2% survival in 2006–2007, with no difference between the types of treatment center. However, for this unique group of diseases, survival is not the unique endpoint. In order to ensure good quality of life after cancer, management of those patients requires specific approaches, designed to reduce the late effects of cancer treatment and improve supportive care.

Neoadjuvant chemotherapy is able to reduce the size of the majority of breast tumours and down-stage axillary-node status. The aim of this study was to assess the prognostic value of persistent node involvement after neoadjuvant chemotherapy. A total of 488 patients with T2–T3, N0–N1 breast cancer treated by neoadjuvant chemotherapy followed by tumour excision and axillary lymph-node dissection between 1981 and 1992 were selected from the Institut Curie database. Median follow-up was 7 years. Overall objective response rate before local treatment was 52% and breast tumour size was reduced in 83% of patients. No pathologic nodal involvement was observed in 46.5% of patients. Patients with ≥ eight positive nodes had a very poor median disease-free survival of only 20 months. Their 10-year disease-free survival rate was 7%, while the 10-year disease-free survival rate for patients with no node involvement was 64%. Median survival for patients with ≥ eight nodes positive was 48 months and the 10-year survival rate was 26% (P < 0.0001). On multivariate analysis, outcome was strongly correlated with pathological nodal status, tumour grade, hormonal receptor status and clinical response of the tumour. In conclusion, patients with extensive nodal involvement after neoadjuvant chemotherapy have a very poor outcome. Second-line treatment should be considered in this population. © 2000 Cancer Research Campaign http://www.bjcancer.com

Given the excellent survival rate of children and teenagers treated for cancer, careful should be given in order to minimize long-term late effects of treatments and to improve quality of life. In this regard, fertility preservation is particularly important. Age, sex and concomitant therapies have an impact on the level of risk of hypofertility, with a stronger risk for chemotherapeutic regimens including alkylating agents, and gonads or hypothalamo-pituitary axis radiotherapy. Assessment of gonadotoxic impact of treatment strategy and fertility preservation techniques are crucial for limiting late effects. The objective of this literature review is to develop guidance for pediatric oncologists and hematologists relative to fertility preservation methods, in children and teenagers receiving gonadotoxic treatment. Specific follow-up after treatment is also proposed.

Differential gene expression revealed by the analysis of total protein patterns was investigated in somatic embryogenesis of Daucus carota L. The aim of this work was to identify markers, and to assess the relationships between induction and different developmental stages of somatic embryogenesis. Proteins extracted from an embryogenic cell suspension and five developmental stages of somatic embryos were separated by two-dimensional gel electrophoresis. Both quantitative and qualitative changes were detected, and the relationships between the protein patterns were visualized using an unrooted tree. The different organs of somatic plantlets, namely root, hypocotyl and cotyledon, were analyzed separately for spatial differences in protein distribution. A comparison of six protein patterns revealed that the variable proteins were modulated according to five profiles, three of which are most relevant. Among the variable proteins, ten were specific to the cell suspension stage and might be assigned either to callogenesis or to embryogenesis induction. Six proteins found only in somatic embryos were shown to fluctuate at different developmental stages and represent morphogenesis markers. Proteins absent during the early stages of embryo development but expressed in the cell suspension stage as well as in the later stages, might be correlated with the presence of 2,4-D. In fact, the unrooted tree revealed that the cell suspension protein pattern was closer to that of somatic plantlets than to earlier stages of embryogenesis. Furthermore, the CS pattern was closer to that of roots, which are auxin inducible, than to the other organ of the plantlet. Therefore, possible effects of exogenous and endogenous auxins on protein synthesis are discussed.

11023Background: Ewing’s sarcoma family of tumorsis a group of rare and aggressive tumors. Data on tumor, clinical presentation and treatment in patients (pts) older than 50 years are limited. Outc...

11000Background: EE99R2Loc (ISRCTN61438620) was conducted in 12 countries, by 4 cooperative groups: GPOH, SFCE/GSF, UK-CCLG, and EORTC. It evaluated effects on event-free (EFS, main endpoint) and o...

Phase II trials demonstrate the activity of cisplatin in patients with refractory Ewing sarcoma family tumours (ESFT) and also the feasibility of giving cisplatin with oral VP16 in a variety of different cancers. This trial was conducted to evaluate the activity and toxicity profile of this combination delivered as outpatient therapy in patients with refractory/relapsed ESFT.Cisplatin was administered on days 1, 8 and 15 and days 29, 36 and 43 (70 mg/m(2)/dose for patients21 years of age and 50 mg/m(2)/dose ≥21 years). VP16 was administered at a dose of 50 mg/m(2) on days 1-15 and days 29-43 inclusive. A three-stage Fleming statistical design was used for analysis.Between January 2003 and October 2006, 45 patients aged between 5 and 46 years (median 19) were enrolled. Thirty-eight were evaluable for response. Patients had previously received one to three lines of chemotherapy (median = one). Seventy-three per cent of the patients had grade 3/4 neutropenia, 20 % developed fever, 40 % had grade 3/4 anaemia, 68 % grade 3/4 thrombocytopenia and 16 % grade 2/3 ototoxicity. Measured response after 2 cycles: 0 CR, 7 PR (18 %), 13 SD (34 %), 18 PD (48 %). There was excellent concordance between unidimensional and bidimensional criteria in 31 of 33 responses (94 %). PFS at 1 year was 39 %, with a median PFS of 6 months. Overall survival at 1 year was 44 %; median survival was 11 months.Cisplatin combined with oral VP16 is well tolerated and has acceptable side effects, but limited clinical activity in refractory/relapsed ESFT.

International audience; Primary malignant bone tumours, osteosarcomas, and Ewing sarcomas are rare diseases which occur mainly in adolescents and young adults. With the current therapies, some patients remain very difficult to treat, such as tumour with poor histological response to preoperative CT (or large initial tumour volume for Ewing sarcomas not operated), patients with multiple metastases at or those who relapsed. In order to develop new therapies against these rare tumours, we need to unveil the key driving factors and molecular abnormalities behind the malignant characteristics and to broaden our understanding of the phenomena sustaining the metastatic phenotype and treatment resistance in these tumours. In this paper, starting with the biology of these tumours, we will discuss potential therapeutic targets aimed at increasing local tumour control, limiting metastatic spread, and finally improving patient survival.

Adolescence and young adulthood can be an extremely stressful time for all concerned. When this period is compounded by the development of cancer, formidable and seemingly insurmountable problems may be perceived. With an annual incidence rate in western populations of around 250–300 per million, cancer in adolescents and young adults (AYAs) is relatively uncommon. In the western countries, five-year survival of patients diagnosed around 1990 exceeded 70%; therefore, many AYAs with cancer may remain fertile. Further advances in therapeutic modalities are creating a generation of AYAs with cancer who can now aspire to the same sexual and reproductive activities as their healthy peers. This then raises the issue of avoidance of undesired pregnancy during and after treatment. This chapter aims to address the contraceptive needs of AYAs undergoing treatment for cancer.

Among all solid tumors breast cancer is the most common cause of meningeal carcinomatosis (MC). The purpose of this study was to analyze clinical and biological responses as well as overall survival in MC patients (pts) of breast primary treated with intrathecal methotrexate (MTX).Single-center retrospective series of MC pts treated between 2000 and 2007. Chemotherapy regimen was: MTX (15 mg/day; day 1-5) and depomedrol (40 mg, day 1) plus leucoverin (12 mg IV or 25 mg PO; day 1-5). Treatment cycles were repeated every 2 weeks. The survival was analyzed according to the characteristics of the tumor considering clinical and cytological response rates to treatment.The median survival was 4.5 months (range 0-53). In multivariate analysis, poor prognostic factors at diagnosis were: Performans status greater than 2 [P = 0.006, RR = 0.33 (0.15-0.71)], more than three chemotherapy regimens before MC diagnosis [P = 0.03, RR = 0.40 (0.19-0.93)], negative hormone receptor status [P = 0.02, RR = 0.4 (0.19-0.90)] and high Cyfra-21-1 level [P = 0.048, RR = 0.09-0.99]. The clinical progression after one cycle and the biological response after two cycles were independently correlated with OS [P0.001, RR = 0.09 (0.02–0.37) and P = 0.003, RR = 3.6 (1.5–8.5), respectively]. A prognostic score designed to define three groups of patients is proposed.Although prognosis of patients with MC is poor, 1-year overall survival rate is 25%. The proposed prognostic score may be helpful in decision but warrants further assessment and validation in prospective trials.

Breast cancer treatment relies on 3 major phenotypical subtypes, including the triple-negative (TN), HER2-positive, and hormone receptor-positive (estrogen receptor/progesterone receptor) ones. We retrospectively determined the clinical and pathologic response rates to intensified taxane-free neoadjuvant chemotherapy according to these phenotypical classes in a series of patients with highly proliferative operable breast cancer, and examined the patterns of recurrence.Patients with early breast cancer with highly proliferative (S-phase fraction4%) operable tumors of3 cm received 4 cycles of intensified neoadjuvant chemotherapy with high-dose cyclophosphamide (doxorubicin 70 mg/m d1, cyclophosphamide 700 mg/m d1/d8, and 5 FU 700 mg/m d1-d5) every 3 weeks.Fifty-five patients were included in the analysis. Patients with TN phenotype experienced a high pathologic complete response (pCR) rate to intensified chemotherapy in comparison with patients with HER2-positive and estrogen receptor/progesterone receptor tumors (47%, 0%, and 12%, respectively). Forty percent of patients with TN breast cancer recurred after a median follow-up of nearly 11 years, but only 22% of those achieving a pCR.A high pCR rate to short intensified neoadjuvant chemotherapy with high-dose cyclophosphamide was achieved in patients with operable highly proliferative TN breast cancer, and pCR was associated with a low rate of recurrence.

La survenue d’un cancer chez un adolescent pose des problemes specifi ques sur le plan medical mais aussi psychologique, scolaire, social ou encore familial. a cette periode de la vie, marquee par une transition delicate de l’enfance vers l’âge adulte, le traitement d’un cancer necessite une reconnaissance et une prise en compte de l’ensemble de ces differents besoins afi n d’aider au mieux l’adolescent et ses proches a traverser cette experience. Cette tâche n’est pas toujours aisee pour les soignants en oncologie qui ne sont pas forcement familiers de ces enjeux lies a la survenue d’un cancer a l’adolescence.

Objective:To improve the palliative care and more effectively meet the needs of young patients and their families at the end of life, the authors investigated the place of death of adolescents and young adults treated in their institution and identified some of the factors influencing the choice of place of death.Methods:The parents and/or partners of adolescents and young adults (15 to 25 years old) who died at Institut Curie (cancer center) between 2000 and 2003 were contacted. Twenty-one families agreed to participate in the interview between October 2005 and April 2006. Analysis of the interviews comprised a descriptive part and a thematic part.Results:Nineteen out of 21 (90%) families declared that they did not really choose their child's place of death due to lack of time. However, all families said that they preferred the hospital. No family attended a bereavement group after their child's death and only 3 families (14%) consulted a mental health care professional. Thematic analysis showed that representations and beliefs concerning life and death at least partly determined the family's capacity to discuss the place of death with their child.Significance of results:Although progress has been made over recent years in France, there is still considerable room for improvement of palliative care to more effectively meet the needs of young patients and their families at the end of life.

Background: The management of malignant germ cell tumors of the ovary (OMGCT) requires multidisciplinary expertise. We analyze the surgical and medical outcomes of a cohort of patients treated for OMGCT. Patients and Methods: Data concerning diagnosis, surgery, and medical decisions were reviewed for all patients seen for postoperative management of OMGCT at the Centre Leon Berard in Lyon and the Institut Curie in Paris between 1985 and 2003. Sixty patients aged 0.4 to 27.9 years (mean 12.8 years) at diagnosis were included. Results: Twenty (53%) of 38 the International Federation of Gynecology and Obstetrics (FIGO) stage I tumors were staged Ix. All stage Ix tumors had been operated by a nongynecologic surgeon. Relapses occurred in 8 of 24 stage I tumors that were observed (0/8 stage Ia; 5/13 stage Ix (P = 0.044) and 3/3 stage Ic) versus 0/14 stage I treated by adjuvant chemotherapy (P = 0.0015). The risk of relapse was significantly increased if patients underwent postsurgical observation ((HR) = 4.5 (95% CI, 1.5 to 13.3)), and when the tumor contained yolk sac tumor (HR = 7.3 (95% CI, 2.3 to 22.7)). There was no significant prognostic value for age, stage, level of tumor markers at diagnosis, type of surgery, and type of chemotherapy. Five-year overall survival was 96.7%, and event free survival was 83.3%. Conclusion: Comprehensive staging after removal of localized OMGCT is crucial. It allows a safe observation strategy in stage la tumors. Patients with stages Ix and Ic tumors may benefit from adjuvant chemotherapy.